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The impact of age on genetic testing decisions in amyotrophic lateral sclerosis
UCL Queen Square Motor Neuron Disease Centre, Department of Neuromuscular diseases, UCL Queen Square Institute of Neurology, London, UK; Maurice Wohl Clinical Neuroscience Institute, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, UK.
Maurice Wohl Clinical Neuroscience Institute, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, UK; Department of Biostatistics and Health Informatics, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, UK; National Institute for Health Research Biomedical Research Centre and Dementia Unit at South London and Maudsley NHS Foundation Trust and King’s College London, London, UK.
Maurice Wohl Clinical Neuroscience Institute, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, UK.
Department of Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
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2022 (Engelska)Ingår i: Brain, ISSN 0006-8950, E-ISSN 1460-2156, Vol. 145, nr 12, s. 4440-4447Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Amyotrophic lateral sclerosis (ALS) is a heterogeneous neurodegenerative syndrome. In up to 20% of cases, a family history is observed. Although Mendelian disease gene variants are found in apparently sporadic ALS, genetic testing is usually restricted to those with a family history or younger patients with sporadic disease. With the advent of therapies targeting genetic ALS, it is important that everyone treatable is identified. We therefore sought to determine the probability of a clinically actionable ALS genetic test result by age of onset, globally, but using the UK as an exemplar.

Blood-derived DNA was sequenced for ALS genes, and the probability of a clinically actionable genetic test result estimated. For a UK subset, age- and sex-specific population incidence rates were used to determine the number of such results missed by restricting testing by age of onset according to UK's National Genomic Test Directory criteria.

There were 6274 people with sporadic ALS, 1551 from the UK. The proportion with a clinically actionable genetic test result ranged between 0.21 [95% confidence interval (CI) 0.18-0.25] in the youngest age group to 0.15 (95% CI 0.13-0.17) in the oldest age group for a full gene panel. For the UK, the equivalent proportions were 0.23 (95% CI 0.13-0.33) in the youngest age group to 0.17 (95% CI 0.13-0.21) in the oldest age group. By limiting testing in those without a family history to people with onset below 40 years, 115 of 117 (98% of all, 95% CI 96%-101%) clinically actionable test results were missed.

There is a significant probability of a clinically actionable genetic test result in people with apparently sporadic ALS at all ages. Although some countries limit testing by age, doing so results in a significant number of missed pathogenic test results. Age of onset and family history should not be a barrier to genetic testing in ALS.

Ort, förlag, år, upplaga, sidor
Oxford University Press, 2022. Vol. 145, nr 12, s. 4440-4447
Nyckelord [en]
age of onset, amyotrophic lateral sclerosis, genetic counselling, genetic testing, motor neuron disease
Nationell ämneskategori
Neurologi
Identifikatorer
URN: urn:nbn:se:umu:diva-203236DOI: 10.1093/brain/awac279ISI: 000859270300001PubMedID: 36162820Scopus ID: 2-s2.0-85143898434OAI: oai:DiVA.org:umu-203236DiVA, id: diva2:1727691
Forskningsfinansiär
Wellcome trust, 102186/B/13/ZHjärnfonden, 2012-0262Hjärnfonden, 2012-0305Hjärnfonden, 2013-0279Hjärnfonden, 2016-0303Hjärnfonden, 2018-0310Hjärnfonden, 2020-0353Vetenskapsrådet, 2012-3167Vetenskapsrådet, 2017-03100Knut och Alice Wallenbergs Stiftelse, 2012.0091Knut och Alice Wallenbergs Stiftelse, 2014.0305Knut och Alice Wallenbergs Stiftelse, 2020.0232Region Västerbotten, 56103-7002829Konung Gustaf V:s och Drottning Victorias FrimurarestiftelseTillgänglig från: 2023-01-17 Skapad: 2023-01-17 Senast uppdaterad: 2023-07-12Bibliografiskt granskad

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